Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model.
BACKGROUND
The aim of this study was to evaluate the effect of an anti-flagellin sub-type monoclonal antibody (anti-fla-a) on Pseudomonas aeruginosa infection in a mouse burn model and to assay bacterial dissemination and invasiveness.


METHODS
After immediate post-burn infection with P. aeruginosa, mortality and morbidity (daily weight changes) were monitored in mice treated with anti-fla-a as compared to untreated mice. Bacterial dissemination and invasiveness were monitored by bacterial counts at the burn site and spleen. Three different timing regimens for anti-fla-a treatment were studied: (a) prophylaxis (pre-infection), (b) therapeutic (post-infection), and (c) combined mode.


RESULTS
Combined regimen of anti-fla-a markedly improved survival of mice infected with P. aeruginosa from 6% to 96% (p<0.0001), similar to treatment with Imipenem. Furthermore, a significant improvement in survival was obtained when anti-fla-a was given prior to (75% survival) or post-infection (50% survival). It reduced bacterial load in the spleen (p=0.01), preventing bacterial sepsis.


CONCLUSIONS
Anti-fla-a is effective in reducing mortality and morbidity in murine P. aeruginosa-infected burn model.
Barnea
Yoav
Y
Division of Epidemiology & Laboratory for Molecular Epidemiology and Antimicrobials Research, Israel. barneay@netvision.net.il
Carmeli
Yehuda
Y
Neville
Lewis F
LF
Kahel-Reifer
Hamutal
H
Eren
Rachel
R
Dagan
Shlomo
S
Navon-Venezia
Shiri
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D002056:Burns / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D005408:Flagellin / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology*; D012867:Skin / Q000473:pathology*; D014946:Wound Infection / Q000382:microbiology
D000911:Antibodies, Monoclonal; D005408:Flagellin